Variant 6-25849417-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098486.2(SLC17A3):c.1319C>G(p.Ala440Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,460,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC17A3
NM_001098486.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

Variant links:

Genes affected

SLC17A3 (HGNC:10931): (solute carrier family 17 member 3) The protein encoded by this gene is a voltage-driven transporter that excretes intracellular urate and organic anions from the blood into renal tubule cells. Two transcript variants encoding different isoforms have been found for this gene. The longer isoform is a plasma membrane protein with transporter activity while the shorter isoform localizes to the endoplasmic reticulum. [provided by RefSeq, Aug 2012]

SLC17A3 links:

LOC124901285 (HGNC:):

LOC124901285 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24813107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A3	NM_001098486.2 link	c.1319C>G	p.Ala440Gly	missense_variant	Exon 11 of 13	ENST00000397060.8	NP_001091956.1	O00476-2
SLC17A3	NM_006632.4 link	c.1085C>G	p.Ala362Gly	missense_variant	Exon 10 of 12		NP_006623.2	O00476-1A0A024QZX7
LOC124901285	XR_007059518.1 link	n.380-10229G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A3	ENST00000397060.8 link	c.1319C>G	p.Ala440Gly	missense_variant	Exon 11 of 13	2	NM_001098486.2	ENSP00000380250.4		O00476-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1460710

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1085C>G (p.A362G) alteration is located in exon 10 (coding exon 9) of the SLC17A3 gene. This alteration results from a C to G substitution at nucleotide position 1085, causing the alanine (A) at amino acid position 362 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0037

.;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.52

T;.;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.011

.;B;B

Vest4

0.23

MutPred

0.62

.;Loss of stability (P = 0.0134);Loss of stability (P = 0.0134);

MVP

0.42

MPC

0.031

ClinPred

0.14

GERP RS

4.5

Varity_R

0.089

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over